Carcinogenesis Advance Access published online on March 4, 2004
Carcinogenesis, doi:10.1093/carcin/bgh131
© 2004 by Oxford University Press
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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1 National Institute of Environmental Health, József Fodor National Center for Public Health, Budapest, H-1097 Hungary
* Corresponding author. E-mail: schoketb{at}okk.antsz.hu.
Received 20 October 2003
; revised 12 January 2004
; accepted 20 February 2004
Smoking is a major risk factor for lung cancer. This comparative study of smoking-related carcinogen-DNA adducts in pulmonary tissues and peripheral blood lymphocytes aims to further explore the primary DNA damaging processes by cigarette smoke in target and surrogate tissues. Samples of tumour and normal peripheral lung tissue, normal bronchial tissue and peripheral blood lymphocytes were obtained from a total of 85 lung cancer patients who underwent lung resection. Bulky DNA adducts were determined by 32P-postlabelling, and polycyclic aromatic hydrocarbon (PAH)-DNA adducts were detected by (±)-7
lung cancer, DNA adducts, 32P-postlabelling, BPDE-DNA chemiluminescence immunoassay, molecular dosimetry, smoking
DNA adducts in tumour, normal peripheral lung and bronchus, and peripheral blood lymphocytes from smoking and non-smoking lung cancer patients: correlations between tissues and detection by 32P-postlabelling and immunoassay
3,
2 Béla Johan National Center for Epidemiology, Budapest, H-1529 Hungary
3 Korányi National Institute of Pulmonology, Budapest, H-1529 Hungary
4 National Cancer Institute, NIH, Bethesda MD, 20892, USA
,8
-dihydroxy-9
,10
-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-DNA chemiluminescence immunoassay (BPDE-DNA CIA) in smaller subsets of tissue samples subject to availability of DNA. Bulky DNA adduct levels ranged between 0.3 and 27.8 adducts/108 nucleotides with mean adduct levels between 2.8 and 11.5 adducts/108 nucleotides. Mean PAH-DNA adduct levels were 2.6-6.2 adducts/108 nucleotides. Significantly higher bulky DNA adduct levels were detected in smokers' lung as compared to non-smokers' (p<0.02). PAH-DNA adduct levels appeared higher in lungs of smokers compared to non-smokers but the difference was not significant. Lung tumour contained on average a 50% lower DNA adduct level compared to normal lung tissue. A statistically significant positive correlation was found between the DNA adduct levels of the corresponding tumour and normal lung tissue samples in both smokers and non-smokers using both methodologies. Bulky DNA adduct levels in normal lung and blood lymphocytes correlated significantly in non-smokers only (r=0.55, p=0.023). In lung tumour DNA samples there was a weak correlation between values obtained by 32P-postlabelling and by the BPDE-DNA immunoassay (r=0.27, p=0.054). However, with normal lung DNA samples, values obtained by the two assays did not correlate.![]()
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